A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo.

Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high-voltage and high-frequency power supply. Eight-week-old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low-dose group), and 180s' CAP (high-dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound-healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low-dose group and high-dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL-6, tumour necrosis factor-α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor-ß in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound-healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.